Rosendaal linear interpolation method appraising of time in therapeutic range in patients with 12-week follow-up interval after mechanical heart valve replacement.

Background: The objective of this study was to evaluate the quality of anticoagulation by the time in therapeutic range (TTR) for patients with 12-week INR follow-up interval. Materials and methods: From January 2018 to December 2020, a selective group of patients who underwent mechanical valve replacement and followed up at our anticoagulation clinic for adjustment of warfarin dose were enrolled. The incidences of complications of anticoagulation therapy were reported by linearized rates. TTR was calculated by the Rosendaal linear interpolation method. Results: Two hundred and seventy-four patients were eligible for this study. The mean age of these patients was 52.8 ± 12.7 years, and 65.7% (180 cases) of them were females. The mean duration of warfarin therapy was 16.7 ± 28.1 months. A total of 1309 INR values were collected, representing 66789 patient days. In this study, the mean TTR was 63.7% ± 18.6%, weekly doses of warfarin were 20.6 ± 6.0 mg/weekly, and the mean monitoring interval for the patient was 53.6 ± 27.1 days. There were 153 cases in good TTR group (TTR ≥ 60%) and 121 cases in poor TTR group (TTR < 60%). The calculated mean TTR in both groups was 42.6% ± 22.1% and 74.8% ± 10.4%, respectively. Compared with the TTR ≥ 60% group, the TTR < 60% group exhibited a more prevalence of female gender (p = 0.001), atrial fibrillation (p < 0.001), NYHA ≥ III (p < 0.001), and lower preoperative left ventricular ejection fraction (LVEF, p = 0.032). In multivariate analysis, female gender (p = 0.023) and atrial fibrillation (p = 0.011) were associated with TTR < 60%. The incidence of major bleeding and thromboembolic events was 2.7% and 1.1% patient-years, respectively. There was one death which resulted from cerebral hemorrhage. The incidence of death was 0.5% patient-years. The difference in anticoagulation-related complications between the TTR < 60% group and the TTR ≥ 60% group was not statistically significant. Conclusion: For patients with stable international normalized ratio monitoring results who are follow-up at anticoagulation clinics, a 12-week monitoring interval has an acceptable quality of anticoagulation. The female gender and atrial fibrillation were associated with TTR < 60%.

Quality evaluation and genetic study of anti-coagulation therapy of warfarin in stable period after mechanical valve replacement / 中国胸心血管外科临床杂志

@#Objective    To evaluate the quality of warfarin anticoagulant therapy in patients with stable stage after mechanical valve replacement surgery, to observe the effect of compound salvia miltiorrhiza tablet on the anticoagulant effect of warfarin in patients after mechanical valve replacement, and to understand the impact of genetic polymorphisms of VKORC1, CYP2C9 and CYP4F2 on warfarin resistance in patients with mechanical valve replacement in the stable period. Methods    From July 2011 to February 2014, 1 831 patients who had ≥ 6 months after mechanical valve  replacement surgery were enrolled at the outpatient follow-up. The basic clinical data were recorded. Anticoagulant therapy uses a target international normalized ratio（INR, 1.60–2.20) and a weekly warfarin dose adjustment strategy. Forty-six patients who needed compound salvia miltiorrhiza tablet were screened and the INR values. Before and after taking tablets were recorded and compared. The patients were divided into three groups according to the percentile of warfarin dosage including a warfarin sensitive patients group, a control patients group, and a warfarin resistance patients group. And 101 of them were selected. TIANGEN blood DNA Kit blood genomic DNA extraction kit was used to extract samples and polymerase chain restriction fragment length polymorphism (PCR-RELP) was used to determine the genotypes of patients. The detected gene loci included CYP4F2: rs2108622C>T locus; VKORC1:1639G>A locus; VKORC1:1173C>T locus; CYP2C9*2: rs1799853C>T locus; CYP2C9*3:1061A>C locus. Results    The time in therapeutic range (TTR) and fraction of time in therapeutic range (FTTR) in the target INR range of the patients included in the study period was 27.2% and 49.4%, respectively, and the TTR and FTTR in the acceptable INR range was 34.25% and 63.36%, respectively. Before and after the addition of compound salvia miltiorrhiza tablets, the INR value was 1.55±0.03 and 1.69±0.30, respectively, and the difference was statistically different (P<0.05). A total of 101 patients with genetic testing, in which the C/T composition of the VKORC1: 1173C>T locus increased in the warfarin sensitivity, contrast and warfarin resistance patients, while the ratio of allelic loci of C/T in CYP2C9*3: 1061A>C loci decreased in turn. There was no difference in the CYP4F2 gene, VKORC1639 gene, and CYP2C9*2 locus. The IWPC model predicts that warfarin dose is only consistent with the actual warfarin dose in warfarin sensitive patients. Conclusion    Relatively low TTR and FTTR are acceptable in patients with stable stage after mechanical valve replacement. It is beneficial to the patients with compound salvia miltiorrhiza tablets in terms of some appropriate patients. VKORC1: 1173C>T site and CYP2C9*3: 1061A>C site mutation is the main pharmacological gene factor of warfarin dose sensitivity and warfarin resistance in stable period after mechanical valve replacement. The IWPC dose prediction model is only consistent with the actual dose of warfarin sensitive patients.

Nanotechnology, an alternative with promising prospects and advantages for the treatment of cardiovascular diseases.

Cardiovascular diseases (CVDs) are one of the most important causes of mortality and affecting the health status of patients. At the same time, CVDs cause a huge health and economic burden to the whole world. Although a variety of therapeutic drugs and measures have been produced to delay the progress of the disease and improve the quality of life of patients, most of the traditional therapeutic strategies can only cure the symptoms and cannot repair or regenerate the damaged ischemic myocardium. In addition, they may bring some unpleasant side effects. Therefore, it is vital to find and explore new technologies and drugs to solve the shortcomings of conventional treatments. Nanotechnology is a new way of using and manipulating the matter at the molecular scale, whose functional organization is measured in nanometers. Because nanoscale phenomena play an important role in cell signal transduction, enzyme action and cell cycle, nanotechnology is closely related to medical research. The application of nanotechnology in the field of medicine provides an alternative and novel direction for the treatment of CVDs, and shows excellent performance in the field of targeted drug therapy and the development of biomaterials. This review will briefly introduce the latest applications of nanotechnology in the diagnosis and treatment of common CVDs.

Ten-year experience of tricuspid valve replacement with the St. Jude medical valve.

Bioprosthetic valves for tricuspid valve replacement (TVR) have become increasingly popular in recent years, but mechanical valves remain valuable, particularly for the patients who want to avoid reoperation for bioprostheses malfunction. The aim of this study was to review our 10-year experience in adult patients who underwent TVR with the St. Jude Medical (SJM) valve. From 2005 to 2015, 265 TVRs with SJM valves were performed at our institution. The mean age at operation was 44.1 ± 9.7 years, and 207 cases (78.1%) were female. The mean follow-up was 4.9 ± 2.7 years. Preoperative atrial fibrillation was present in 199 cases (75.1%) and ascites in 26 (9.8%). Of all cases, 88.7% were characterized as New York Heart Association class III or IV. The hospital mortality was 6.4%. There were 9 deaths (3.8%) during late follow-up. The overall survival rates were 89.2% ± 2.2% at 5 years and 86.6% ± 2.9% at 10 years. The linearized rates of valve thrombosis and bleeding events were 0.8%/patient-year and 1.5%/patient-year, respectively. Three cases (1.3%) were reoperated due to prosthetic valve thrombosis. There was no reoperation for sperivalvular leakage and structural failure. The freedom from reoperation was 98.6% ± 0.8% at 5 years and 98.6% ± 0.8% at 10 years. The SJM valve in the tricuspid position is a reliable mechanical prosthesis with a low rate of valve thrombosis and reoperation. It is a reasonable choice for the patients who require mechanical valve replacement in the tricuspid position.

Excessive bleeding and reexploration after cardiac surgery is a simple and worth thinking about issue / 中国胸心血管外科临床杂志

@#The incidence of postoperative excessive bleeding and reexploration is relatively high, and it will bring a series of serious complications, such as an additional surgery, a longer intensive care unit stay, longer time on mechanical ventilation, an increase need of allogeneic blood product transfusions and increased mortality. However, the understanding of postoperative excessive bleeding and reexploration in China is significantly different from the international level, and the understanding of postoperative excessive bleeding and reexploration after cardiac surgery in clinical work is still not enough. This review will focus on some problems, such as related factors analysis of postoperative excessive bleeding, hemostatic process optimization and the serious complications of reexploration after cardiac surgery.

Primary Left Atrial Osteosarcoma.

Primary cardiac osteosarcomas are rare entities, mostly arising from the left atrium. Because of their rarity, few reports have described this uncommon lesion. We herein report a case of primary cardiac osteosarcoma originating from the left atrium in a 34-year-old woman, who underwent tumor debulking surgery and died 3 months after being diagnosed.

Echocardiographic assessment of long-term hemodynamic characteristics of mechanical mitral valve prostheses with different mitral valvular diseases.

Mitral stenosis (MS) and mitral insufficiency (MI) have different pre-operative hemodynamic characteristics. However, it is unclear if there are differences in long-term echocardiographic characteristics of MS and MI patients after mechanical mitral valve replacement. This study is to compare long-term echocardiographic results of mechanical mitral valve prostheses between MS and MI patients. From January 2003 to January 2009, a total of 199 consecutive patients were recruited in this study. Patients were classified as group MS (n = 123) and MI (n = 76) according to the manifestation of mitral valvular disease. The mean age for patients was 50.1 ± 10.5 years and follow-up time was 7.2 ± 2.0 years. The MS after operation were more likely to experience atrial fibrillation (p = 0.002). The New York Heart Association (NYHA) class in MI showed a greater improvement (p = 0.006) than in MS. The left ventricular end-diastolic dimension (LVEDD) (p = 0.010) and stroke volume (SV) (p = 0.000) in MI were still larger than that in MS patients. These differences did not disappear with time after operation. The long-term echocardiographic results of mechanical mitral valve prostheses between MS and MI patients are significantly different. Over a long-term follow up, MI patients still have a larger LVEDD and SV than MS, and associated with a greater improvement of NYHA class.

Progress of anticoagulant therapy of the patients with mechanical prosthetic valve replacement / 中国胸心血管外科临床杂志

@#The patients with mechanical prosthetic valve replacement need anticoagulant therapy for all their life. The incidence of thromboembolism and anticoagulation-related bleeding events still account for major postoperative complications after mechanical heart valve replacement. Most of the complications happen in the first half year after operation. Therefore, early anticoagulation therapy is very important. Of course, so far most guidelines focus stating their opinions on long-term anticoagulant therapy. However, there is no consensus about anticoagulant therapy in the early period of postoperation. In this review, we summarize early anticoagulant therapy of the patients with mechanical heart valve replacement through consulting domestic and abroad relevant research in recent years and give an overview of the present situations of early anticoagulant therapy.

Surgical repair of inferior sinus venosus defects: a novel approach with unsnared inferior vena cava.

BACKGROUND: Inferior sinus venosus defects (SVD) are very rare and difficult to image from transthoracic echocardiography. Surgical errors were occasionally reported in the repair of inferior SVDs. RESULTS: The authors have operated on 12 inferior SVD patients using bicaval cannulation with unsnared inferior vena cava (IVC) and proved successful. CONCLUSION: This technique guaranteed a better exposure of surgical field and facilitate identifying the anatomical relationship between lower part of the SVD and IVC orifice, thus avoiding postoperative IVC - left atrial shunt and other surgical mistakes.

Detection and diagnosis of iatrogenic inadvertent diversion of partial inferior vena cava into the left atrium by transesophageal echocardiography during large posteroinferior surgical atrial septal defect closure.

Iatrogenic diversion of the inferior vena cava (IVC) into the left atrium (LA) is usually reported as a rare complication following large posteroinferior atrial septal defect (ASD) surgery. It may cause acute or chronic hypoxemia, and other potentially life-threatening complications such as stroke. We present a case in which the ASD patch straddled the IVC entrance diagnosed immediately by transesophageal echocardiography (TEE) during the period of patient separated from cardiopulmonary bypass, avoiding the related complications. Our report further underlines the important role of TEE to monitor and guide ASD surgical management, especially secundum ASD with inferior extension or inferior sinus venosus defects, for the early diagnosis of iatrogenic surgical errors.

[Long-term characteristics and clinical significance of echocardiogram in patients after mechanical prosthesis aortic valve replacement].

The main purpose of this study is to observe and analyze the characteristics and the clinical significance of long-term echocardiogram data in patients after mechanical aortic valve replacement operation. Fifty-five cases were recruited over 5 years after mechanical aortic valve replacement operation, with complete echocardiogram examination profiles. The 55 subjects were divided into predominate aortic stenosis group and predominate aortic regurgitation group, based on preoperative examinations. And another way of division was also carried out that according to the effective orifice area index (EOAI), the subjects were divided into three groups, i. e. , severe prosthesis-patient mismatch (PPM) group, moderate PPM group, and non PPM group. Characteristics of long-term echocardiogram data of the subjects were analyzed. Patients with aortic stenosis showed significantly decreased thickness of intraventricular septum and left ventricular posterior wall about half a year after operation (P < 0.05). Half a year after operation, patients with aortic regurgitation showed decreased left ventricular internal dimension diastole and left ventricular internal dimension systole, and increased ejection fraction (P < 0.05). Differences in mean aortic valve pressure gradient, forward blood flow across the aortic valves, and ejection fraction were not significant among those with severe PPM, moderate PPM, and non PPM groups (P > 0.05). Number of cases of ascending aorta dimension increased as time goes on and pathogenesis of other valve diseases. A conclusion could be drawn that the heart function of patients with aortic valve disease could be improved after mechanical aortic valve replacement operation, but pathologies in other valves and ascending aorta might be increased, and therefore periodical postoperative echocardiogram evaluation with long-term pharmaceutical therapy could be necessary.

Verification of pharmacogenetics-based warfarin dosing algorithms in Han-Chinese patients undertaking mechanic heart valve replacement.

OBJECTIVE: To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. METHODS: We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with mechanic heart valve replacement were consecutively recruited between March 2012 and July 2012. The predicted warfarin dose of each patient was calculated and compared with the observed initial and stable warfarin doses. The percentage of patients whose predicted dose fell within 20% of their actual therapeutic dose (percentage within 20%), and the mean absolute error (MAE) were utilized to evaluate the predictive accuracy of all the selected algorithms. RESULTS: A total of 8 algorithms including Du, Huang, Miao, Wei, Zhang, Lou, Gage, and International Warfarin Pharmacogenetics Consortium (IWPC) model, were tested in 181 patients. The MAE of the Gage, IWPC and 6 Han-Chinese pharmacogenetics-based warfarin dosing algorithms was less than 0.6 mg/day in accuracy and the percentage within 20% exceeded 45% in all of the selected models in both the initial and the stable treatment stages. When patients were stratified according to the warfarin dose range, all of the equations demonstrated better performance in the ideal-dose range (1.88-4.38 mg/day) than the low-dose range (<1.88 mg/day). Among the 8 algorithms compared, the algorithms of Wei, Huang, and Miao showed a lower MAE and higher percentage within 20% in both the initial and the stable warfarin dose prediction and in the low-dose and the ideal-dose ranges. CONCLUSIONS: All of the selected pharmacogenetics-based warfarin dosing regimens performed similarly in our cohort. However, the algorithms of Wei, Huang, and Miao showed a better potential for warfarin prediction in the initial and the stable treatment phases in Han-Chinese patients undertaking mechanic heart valve replacement.

Differential regulation of mitogen-activated protein kinase signaling pathways in human with different types of mitral valvular disease.

BACKGROUND: Mitogen-activated protein kinases (MAPKs) are considered to play a prominent role in cardiac development, function, and pathogenesis. The different types of mitral valvular disease (MVD), including mitral regurgitation (MR) and mitral stenosis (MS), have different underlying pathophysiologic changes, but the precise intracellular signal transduction mechanisms are not clear. Thus, we investigated the differential regulation of MAPK signaling pathways in humans with different types of MVD. METHODS: Left atrial appendage tissue samples from 32 patients with MVD who were undergoing mitral valve replacement surgery were studied. Serum angiotensin II concentrations were measured using enzyme-linked immunosorbent assay. The expression of MAPK pathway-related genes and proteins was assessed using quantitative polymerase chain reaction, Western blot, and immunohistochemistry. RESULTS: Echocardiography showed that patients with MS had a greater left atrial pressure overload than those with MR. The relative amounts of angiotensin II, extracellular signal-regulated kinase 1, p38α, c-Jun N-terminal kinase 2, c-Fos, activating transcription factor 2, and c-Jun mRNA were significantly upregulated in those with MS compared with those with MR (P < 0.05). The serum angiotensin II concentrations were significantly increased in those with MS compared with those with MR (P = 0.017). Substantial changes in the phosphorylated forms of the MAPK proteins were detected. Phosphorylated extracellular signal-regulated kinase 1/2, and phosphorylated p38 were significantly increased in those with MS compared with those with MR (P < 0.001), and phosphorylated c-Jun N-terminal kinase in the MR group was significantly greater than that in the MS group (P < 0.001). Histologically, more serious myocardial cells losses, myolysis, and interstitial fibrosis were detected in the MS group. CONCLUSIONS: The different types of MVD have different hemodynamic characteristics, and different MAPK pathways were activated in the MR and MS groups, which could lead to diverse left atrial histologic changes.

Circulating and local renin-angiotensin-aldosterone system express differently in atrial fibrillation patients with different types of mitral valvular disease.

Mitral valvular disease is strongly related to atrial fibrillation (AF), but the different types of mitral valvular disease have a different prevalence of AF. In this study we explored the expressions of the circulating and local renin-angiotensin-aldosterone system (RAAS) in order to determine the relationship between circulating and local RAAS expressions and its effects on AF in different types of mitral valvular disease patients. Our study group consisted of 24 mitral valvular disease patients scheduled for mitral valve replacement surgery. Peripheral blood samples and left atrial appendage tissue samples were obtained from all patients. Radioimmunoassay was performed to assess the expression levels of circulating and local renin, angiotensin II and aldosterone. In mitral valvular diseases, linear correlation analyses were done for local and circulating renin, angiotensin II and aldosterone; the p values were 0.979, 0.518 and 0.125, respectively. Expression levels of local angiotensin II, circulating angiotensin II and local aldosterone were significantly increased in the AF group compared with sinus rhythm; the p values were 0.023, 0.042 and 0.035, respectively. In mitral stenosis patients, AF was primarily associated with local angiotensin II (p=0.010), as well as being associated with circulating angiotensin II (p=0.038). In mitral regurgitation patients, AF was only significantly associated with local angiotensin II (p=0.038). Circulating and local RAAS expressions are associated with AF in mitral valvular disease patients. The levels of circulating and local RAAS expressions were different in AF patients with different types of mitral valvular diseases. The differentiation of circulating and local RAAS expression levels in AF patients between different types of mitral valvular disease can potentially improve the specific pharmacological interventions outcomes for these patients.

Eisenmenger syndrome complicated by pulmonary artery dissection.

This report describes a 40-year-old male patient diagnosed with pulmonary artery dissection involving both the left and right branches. The patient also had Eisenmenger syndrome secondary to an uncorrected patent ductus arteriosus. Diagnosis was facilitated through the use of transthoracic echocardiography and computed tomography. Due to the lack of definite guidelines for the optimal treatment strategy of this condition together with the poor condition of the patient, medical management was elected. Not surprisingly, the patient died suddenly only 7 days after the presentation.

Different structural remodelling in atrial fibrillation with different types of mitral valvular diseases.

AIMS: The aim of this study was to determine the relationship between atrial structural remodelling and atrial fibrillation (AF) for different types of mitral valvular diseases (MVDs). METHODS AND RESULTS: Left atrial appendages tissue samples were obtained from 24 patients with MVDs undergoing mitral valve replacement surgery. Masson's trichrome staining and immunohistochemical staining were performed to assess the extent of the fibrosis. Ultrastructural changes in left atrial appendages were examined by electron microscope. The degree of fibrosis showed significant increases in patients with AF compared with patients with sinus rhythm (SR) (P = 0.023). The collagen volume fraction (CVF) of fibrosis significantly increased in mitral stenosis and atrial fibrillation (MS-AF) compared with the mitral regurgitation and atrial fibrillation (MR-AF) group (P = 0.043). Collagen Type I levels were significantly increased in AF patients with mitral stenosis compared with AF patients with mitral regurgitation (P = 0.043). Different CVF of Matrix metalloproteinases-2 was present between the MS-SR group and the MS-AF group (P = 0.001). Electron microscopy revealed normally structured sarcomeres with a predominance of loosely packed cardiomyocytes in samples from patients with SR. Fibrotic bands, which tended to separate individual cardiomyocytes, were apparent in samples from patients with AF. CONCLUSION: Atrial structural remodelling is associated with AF patients with MVDs. Different heart rhythm statuses with different types of MVDs are associated with variable atrial structural remodelling. Different atrial structural remodelling is a mechanism that may contribute to the increased risk of AF with MVDs.

[Doppler echocardiographic assessment of CarboMedics prosthesis in patients with mitral valve replacement].

OBJECTIVE: To evaluate the CarboMedics (CM) prosthesis function two years after mitral valve replacement, and to compare the effective orifice area (EOA) calculated by pressure half-time (PHT) method and continuity method (CON). METHODS: Forty nine patients who underwent isolated mitral valve replacement with a CM prosthesis were recruited in this study, which included 13 cases of 25 mm CM prosthesis and 36 cases of 27 mm CM prosthesis. Two years after the mitral valve replacement, transthoracic echocardiography (TTE) was performed, measuring left ventricular ejection fraction (LVEF), stroke volume mean gradient (SV), PHT, peak early mitral diastolic velocity (E velocity), mean gradient (MG), time-velocity integral of left ventricular outflow tract/time-velocity integral of mitral valve prosthesis (TVI(MVP)/TVI(LVOT)). The function of the prosthetic valve was considered normal when PHT < 130 ms, E velocity < 2.0 m/s and TVI(MVP)/TVI(LVOT) < 2.2. RESULTS: More than half (53.1%) of the patients had normal function of the prosthetic valve. No significant differences were found in PHT, MG, TVI(MVP)/TVI(LVOT), EOA or IEOA between the patients with 25 mm valve and the patients with 27 mm valve (P > 0.05). But the patients with 25 mm valve had higher E velocity than the patients with 27 mm valve (P < 0.05). The PHT method produced greater EOA than by the CON method (P < 0.05). CONCLUSION: The function of CM prosthesis is acceptable two years after the mitral valve replacement, with most patients having PHT < 130 ms, E velocity < 2.0 m/s and TVI(MVP)/TVI(LVOT) < 2.2. PHT method produces greater EOA than CON method.